• 专利附录
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    • 专利摘要:
    Pyrimido-2-benzazepine der allgemeinen Formel worin A eine der Gruppen R1 Wasserstoff, Chlor, Brom, niederes Alkyl, die Gruppe NR4R5, die Gruppe -CH2-CO-R7, die Gruppe -NH(CH2)mNR8R9, Hydroxy, niederes Alkoxy, Mercapto oder niederes Alkylmercapto, R2 Wasserstoff, Amino oder Di-(nieder)-alkylamino, R Wasserstoff, niederes Acyloxy oder Hydroxy, X Wasserstoff, Halogen, Trifluormethyl, Aethyl, a-Hydroxyäthyl oder Acetyl, Y Wasserstoff oder Halogen, R4 und R5 je Wasserstoff oder niederes Alkyl oder, zusammen mit dem Stickstoffatom, einen 5- bis7-gliedrigen Heterocyclus, welcher ein Sauerstoff-oder Schwefelatom oder die Gruppe N-Niederalkyl enthalten kann, R7 Wasserstoff, niederes Alkoxy oder NR8R9, R6 und R9 je Wasserstoff oder niederes Alkyl, n 0 oder 1 und m 1 bis 7 bedeuten, mit der Massgabe, dass (i) mindestens eines von R1 und R2 Wasserstoff ist; (ii) wenn R3 niederes Acyloxy oder Hydroxy bedeutet, A Gruppe (a), X Wasserstoff, Halogen, Trifluormethyl, Aethyl oder Acetyl und, wenn R1 die Gruppe -NH(CH2)mNR8R9 bedeutet, R' und R9 je niederes Alkyl bedeuten; (iii) wenn A Gruppe (d) und R1 die Gruppe -NH(CH2)mNR8R9 bedeuten, R' und R9 je niederes Alkyl bedeuten; und (iv) wenn n 1 bedeutet, R1 Wasserstoff, niederes Alkyl, niederes Alkoxy, Chlor, Brom oder die Gruppe -CH2-CO-R7 (worin R7 obige Bedeutung besitzt) und A Gruppe (a) oder (b) bedeuten; und pharmazeutisch akzeptable Säureadditionssalze davon sind neu und pharmakologisch verwertbar als Anxiolytika und Sedativa. Diese Verbindungen und Salze können nach verschiedenen Methoden ausgehend von teilweise neuen Zwischenprodukten hergestellt werden.
    公开号:SU1181547A3
    申请号:SU802879255
    申请日:1980-02-05
    公开日:1985-09-23
    发明作者:Йан Фрайер Родней；Вашбэрн Гильмен Нормэн；Джон Трибульски Ойген；Вальзер Армин
    申请人:Ф.Хоффманн-Ля Рош Унд Ко,Аг (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to new pyrimido-2-benzazepine derivatives, which can be used in medicine as a sedative and fear-reducing means.
    The preparation of pyrimidines by cyclization reactions using guanidine derivatives, thiourea or 8-lower alkylthiourea 03-5 is widely described in the literature. The purpose of the invention is to create, on the basis of a known method, a method of producing new compounds with valuable pharmacological properties with improved action.
    The goal is achieved, according to the method of obtaining pyrimido2-benzazepins of the general formula
    where A is one of the groups
     amino or di-alkylamino; X is hydrogen or halo. Y is hydrogen or .halogen of their pharmacologically compatible acid addition salts, for (0.015 mol) of methylate nltrn. After 10 minutes stirring, 30 ml of methylene chloride is added and the mixture is continued to stir. After 2 hours, another 0.8 g (0.015 mol) of sodium methoxide and 0.7 g (0.0075 mol) of acetamidine hydrochloride are added. After another 2 hours, 0.015 mol of sodium methoxide and 0.0075 mol of acetamiding hydrochloride are added once more and the mixture is stirred and the mixture is stirred at room temperature overnight. After diluting the mixture with 50 ml of methylene chloride, it is washed with water, dried over sodium sulfate and evaporated under reduced pressure. After dissolving the residue in 20 ml of thermal hexane and cooling, crystallization occurs. By evaporation of the solvent, one more portion of the product is obtained. Recrystallization from hexane (charcoal) gives whitish crystals with so pl. 120-122 ° C.
    Example 4. 9-Chloro-7- (2-fluorophenyl) -2-methyl-5H-pyrimido 5,4-d 2} -benzazepine.
    To a suspension containing 5.1 g (0.015 mol) of 8-chloro-1- (2-fluorophenyl) 3, A-dihydro-4-t (dimethylamino) methylene-5H-2-benzazepin-5-one and 2,1 g (0.0225 mol) of acetamiding hydrochloride in 150 ml of methanol, stirred at room temperature in argon, is added in one portion to 2.4 g (0.045 mol) of sodium methoxide. After a 10 minute run, 90 ml of methylene chloride are added and stirring is continued. After 2 hours, another 2.4 g (0.045 mol) of sodium methoxide and 2.1 (0.0225 mol) of acetamidine hydrochloride are added. After a 2-hour interval, repeat the addition, which includes 0.045 mol of sodium methoxide and 0.0225 mol of acetamiding dichloride, and continue to stir the mixture overnight at room temperature. After diluting the mixture with 150 ml of methylene chloride, it is washed with water, dried over sodium sulfate and evaporated under reduced pressure. Recrystallization of the residue from hexane (charcoal) gives white crystals with m.p. 104-107 S.
    Example 5. 9-Chloro-7- (2fluorophenyl) -5H-pyrimido 5,4-d3 (2 benzazepin-2-amine and 9-chloro-7- (2fetrophepmyl) -N, N-dimethyl-5H-pyrimyl-f5, 4-d 3 23-be zazepin-2-amine.
    A solution containing 7.0 g (0.0204 mol) o-chloro-1- (2-fluorophenyl) 3,4-DIHIDRO-4- (dimethylamio) methylene-5H-2-benzazepin-b-she and 3.5 g (0.0833 mole-) cyanamide in 300 ml abs. Zanol, heated for 18 hours under reflux and evaporated to dryness. The residue is washed with water, filtered and twice crystallized from methanol to give the N, N-dimethylamino compound. The filtrates are concentrated, the filtrate is recrystallized from methanol to obtain the amino compound. The filtrates are evaporated, dissolved in dichloromethane and chromatographed on Florisil. The column was eluted with dichloromethane, which was evaporated, crystallized from methanol, and another portion of the N, N-dimethylamino compound was obtained. A sample of this product is recrystallized from dichloromethane and ether to obtain needles with mp. 175-180 C. Then the column is eluted with a 5% solution of ether in dichloromethane and ether. The ether fraction is evaporated and crystallized from methanol to obtain another portion of the amino compound, part of which is recrystallized from methanol to produce a white prism of white crystals 9-chloro-7- (2-Ltorophenyl) 5H-pyrimido-1 5, 4-dj 2 - benzazepin-2amina with m.p. 242-247 0 containing 0.2 g (0.5 mmol) of N, N-dimethylamino compound in 5 ml of methanol, 0.05 g (0.5 mol) of methanesulfonic acid was added. Methanol is evaporated, and the oil is crystallized from isopropanol and recrystallized from methanol and ether to obtain yellow prismatic 9-chloro-7- (2-fluorophenyl) N, N-dimethyl-5H-pyrimide 5, 2 benzazepin-2-amine crystals with t .pl. 190-195 0
    Example 6. 9-Chloro-7- (2-chlorophenyl) -2-methyl-5H-pyrimido 5,4-dJ 2 benzazepine.
    5.5 g (58 mmol) of acetamidine hydrochloride and 15 ml (62 mmol) of a 4.12 M ethanol solution of sodium methylate are added in 5 equal portions over 3 hours to a solution containing 3.5 g (10 mmol) of 8-chloro- 1- (2-chlorophenyl) -3,4-dihydro-4 (dimethylamino) methylmer-5H-2-benzazepin-5-one in 140 m of methanol and 140 ml of methylene chloride. The mixture is diluted with water and extracted with methylene chloride. The methylene chloride solution is washed with water and dried with anhydrous sodium sulfate, after concentration of which under reduced pressure, a yellow oil is obtained. The oil is dissolved in 10 ml (10 mmol) of a 1 M methanol solution of methane sulfonic acid to give a salt, which is precipitated by addition of ether, after which yellow prismatic crystals are obtained with mp. 197-198 C. Recrystallization from a mixture of methanol and ether gives yellow prismatic crystals with m.p. 197-198C. Pr and im p 7. 9-chloro-7- (2-chlorophenyl) -5H-pyrimido 5,4-b. Benzase pin. 21 g (200 mmol) of formamidine acetate and 32.5 ml (135 mmol) of a 4.12 M methanol solution of sodium methylate are added in five equal portions over 3 hours to a solution of 7.2 g (20 mmol) of 8-chloro- 1- (2-chlorophenyl) 3, 4-dihydro-4- (dimethylamino) methylene -5H-2-benzazepin-5-one in 270 ml of methanol and 270 ml of methyl chloride. The solution is diluted with water, extracted with methylene chloride, washed with water , dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a yellow oil. After purification by column chromatography (100 g of silica gel), the solvent is methylene chloride and ethyl acetate in a 1: 1 ratio. The desired product is obtained with mp. 122-124 C. Recrystallization from ether gives light yellow prismatic crystals with m.p. 122-125 0. Example 8. 9-chloro-7- (2-chlorophenyl) -2-isopropyl-5H-pyrimido 5,4d C23-benzazepine. A mixture containing 3.5 g (10 mmol) of t- (2-chlorophenyl) -3,4-dihydro-4- (dimesh1amino) methylene -5H-2-benzazepin-5-one, 4.8 g (40 mmol) isobutyramidine hydrochloride, 10 ml (41 mmol) (V) of a 4.12 M methanol solution of sodium methylate and 100 ml of methanol, stirred for 2 hours at room temperature. The mixture is diluted with water and extracted with methylene chloride. The methylene chloride solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a yellow oil. Crystallization of the oil with ether gives a light yellow substance with mp. 127-T29C. Recrystallization from a mixture of ether and petroleum ether gives colorless rod-shaped crystals with m.p. 127-129 ° C, Example 9. 2-Amino-9-chloro 7- (2-chlorofensh1) -5H-PYRIMIDO GZ, 4-d f2 3-benzazepine. 14.4 g (80 mmol) of guanidine carbonate and 20 ml (82 mmol) (V) of a 4.12 M methanol solution of sodium methylate are added in equal portions over 90 minutes to a solution containing 3.6 g (10 mmol) 8-chloro-1- (2-chlorophenyl) -3,4-dihydro-4- (dimethylamino) methylene J-5H-2 benzazepin-5-one in 100 ml of methanol. The mixture is diluted with water and extracted with methylene chloride. The methion chloride solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure. to give a yellow oil. Crystallization of the oil with methylene chloride gives a white solid with so pl. 240-241 C. Recrystallization from a mixture of ether and methylene chloride gives colorless needles with mp. 240-241 C. Example 10. 7- (2-Chlorophenyl) 2-methyl-5H-p-Irimido C5, j-benzazepine-methanesulfonate. 7.2 (76 mmol) of acetamidine hydrochloride and 18 ml (80 mmol) of 4.46 M of methanol solution of sodium methylate are added in equal portions over 3 hours to a solution of 4.5 g (14 mmol) of 1- (2-chlorophenyl) 3, 4-dihydro-4- (dimethylamino) -methylene —5H-2-benzazepin-5-one in 180 ml of methanol and 180 ml of methylene chloride. The mixture is diluted with water and extracted with methylene chloride. The methylene chloride solution is washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a yellow oil. The oil is dissolved in a mixture containing 15 ml of isopropanol and 1.3 g (14 mmol) of methanesulfonic acid, after which isopropanol is removed under reduced pressure. The residue is crystallized from a mixture of ether and methylene chloride to obtain a light yellow solid with so pl. 147-151 C. Recrystallization from a mixture of ether and methylene chloride gives yellow prismatic crystals in the form of a hemihydrate with mp. 159-1BS Example 11. 2-Methyl-7-phenyl 5H-pyrimido 5,4-in C2-benzaeepine Dihydrechloride, 9.0 g (95 mmol) acetamidine hydrochloride and 22.5 ml (0.2-0.1 mill) A, A6 M methanol solution of sodium methylate is added in five equal portions over 3 hours to a solution containing A, 5 g (15 mmol) of 1-phenyl-3, A-dihydro-4 (dimethylamino) methylene-5H-2-6eH 3 azepin-5 - it in 180 ml of methanol and 180 ml of methylene chloride. The mixture is diluted with water and extracted with methylene chloride. The methylene chloride solution is washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give an oil, which is dissolved in an excess of 6% methanol hydrogen chloride. The solvent is then removed to dryness under reduced pressure. The residue is crystallized from a mixture of ether and methylene chloride to obtain a white solid with so pl. 211-221 0. Recrystallization from a mixture of methanol and ether gives flocculent white crystals with m.p. 217-227 C. Example 12. 9-Chloro-7- (2-chloro-phenyl) -5H-pyrimidoC5,4-d G2-benzo PIN-2-TIOL. A mixture containing 2.8 g (7.8 mmo 8-HLOR-1 (2-chlorophenyl) -3,4-dihydro-4 C (dimethylamino) methylene 3-H-2-benzaz pin-5-one, 2.8 g (37 mmol) of thiourea and 8.0 ml (32 mmol) of 4.0 ml of methanol and sodium methylate in 80 ml of methanol, stirred 18 at room temperature. The mixture is diluted with water and extracted with ether. The aqueous layer is neutralized with acetic acid and extracted with methylene chloride. The methylene chloride solution is dried over anhydrous sodium sulphate and concentrated under p under reduced pressure to give a yellow solid with mp 238-239 C. After over Crystallization from tetrahydrofuran gives yellow crystals with mp 232-234 C. Example 13. 9-Chloro-7- (2-ft, phenyl) -5H-pyrimidoC5,4-d C2-benz A mixture containing 34.2 g (0.1 mol) 8-chloro-3,4-dihydro-1- (2-fluorophenyl) 4- {(dimethylamino) methylene 7-5H-2 benzazepin-5-one, 62.4 g (0.6 mol) of formamidine acetate and 35 g (0.63 mol) of sodium methylate in 700 ml of methanol are stirred for 3 hours at room temperature, bubbled through a solution of nitrogen. The mixture is diluted with water and extracted with methylene chloride. The methylene chloride solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a red oil. The oil is suspended in boiling hexane, and the hexane solution is decanted. After cooling, collect the desired product by filtration. Recrystallization from cyclohexane gives whitish crystals with so pl. 123-125 C. Example 14. 2-Amino-9-chloro-7- (2-: fluorophenyl) -5H-pyrimido 5,4-d j 2 -benzazepin-6-oxide. Within 2 hours, to a solution containing 7.0 g (20 mmol) of 8-chloro-1 (2-fluorophenyl) -3,4-DIHIDRO-4- (dimethylamino) methyl-5H-2-benzazepin 5-one-2- oxide in 210 ml of methanol, 28 g (150 mmol) of guanidine carbonate and 38 ml (150 mmol) of 4.09 M sodium methylate solution are added in two equal portions. The mixture is diluted with water and extracted with methylene chloride. The methylene chloride solution is dried with anhydrous sodium sulfate and concentrated under reduced pressure to obtain a red solid. By recrystallization from a mixture of methanol and ethyl acetate, the expected product is obtained in the form of yellow needles with m.p. 320-323 s. Example 15. 9-Chloro-7- (2-chlorofenil) -2-methyl-5H-pyrimido T5,4-dUG2 3-benzazepin-6-oxide. A mixture containing 1 g (2.8 mmol) of 8-chloro-1- (2-chlorophenyl) -4-C (dimethylamino) methylene-3,4-dihydro-5H-2 benzazepin-5-one-5-oxide, 1 , 0 g (11 mmol) of acetamidine hydrochloride and 2.0 ml (9.9 mmol) of a 4.46 M sodium methoxide methanol solution in a mixture of 20 ml of methanol and 20 ml of methylene chloride, stirred at room temperature for 2 hours. The mixture is diluted with water and extracted with methylene chloride. The methylene chloride solution is washed with water, dried with sodium sulfate free, and concentrated to dry under reduced pressure. By recrystallization of the residue from a mixture of ether and methylene chloride I get a colorless solid product with so pl. 215-21bs. Example 16. 9-Chloro-7- (2 chlorophenyl) -ZH-pyrimido 5,4-dJ 2 benzapene. A mixture containing 90.5 g (0.25 mol) of 8-chloro-1- (2-chlorophenyl) 3, 4-DIHIDRO-4- (dimethylamino) methylene 3-5H-2-benzazepin-5-one, 100 g ( 0.96 mol) formamidine acetate and 1.0 formamide, heated for 16 h in a steam bath. The mixture is cooled to, the resulting precipitate is collected by filtration. The precipitate is washed with water and dried until it reaches the set weight, to obtain crystals with m.p. 120-121 ° C, whitish color. Example 17. 9-Chloro-7- (2-fluorophenyl-5H-pyrimido) -5,4-e 2-benzase pin 6-oxide. A mixture containing 0.4 g (1.1 mmol 8-chloro-1- (2-fluorophenyl) -3,4-dihydro-4-rdimethylamino) -methylene-5H-2-ben azepin-5-one-2-o1 side, 1.0 g (9.6 mmol formamide acetate and 20 ml formamide, heated on the steam bath for 6 hours. The mixture is drunk on ice and extracted with methylene chloride. The methylene chloride solution is washed with water, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue is crystallized with addition mixtures of ether and methylene chloride, obtaining crystals with a whitish color, mp 186-188 C. Example 18. 9-Chloro-7- (2 chlorophenyl) -5H-pyrimido 5,4-d 2 benzazepin-6-ca Seed. A mixture containing 0.4 g (1, 1 mmol of 8-chloro-1- (2-chlorophenyl) -3,4-dihydro4- (dimethylamino) methylene2-5I-2benzazepin-5-one-oxide and 1.0 g (9.6 mmol) of formamidine acetate in .20 ml of formamide is heated for 7 hours in a steam bath. The mixture is poured on ice and extracted with methylene chloride. The methylene chloride solution is washed with water, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue is triturated with ether get a solid product with so pl. 215-217 ° C whitish. Example 19. 9-Chlpr-7- (2fluorophenyl) -5H-pyrimido 5,4-djf2 Benzazepin-2-thiol-6-oxy. A mixture containing 1.5 g (4 mmol1) of 8-chloro-1- (2-fluorophenyl) -3,4-dihydro4- (dimethylamino) methylene 3-5H-2-6cii4azepin-5-one-2-oxide, 1 , 5 g (20 mmol1) of thiourea and 5 ml of 4 M sodium methoxide solution in 30 ml of methanol are stirred for 5 hours at room temperature. The mixture was poured into water and extracted with methylene chloride. The aqueous solution is acidified with acetic acid and extracted with methylene chloride. The methylene chloride solution is dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue is triturated with methylene chloride to obtain an orange solid color solid. Recrystallization from methylene chloride gives the product as an orange crystal with so pl. 323-325 ° С (with expansion). Example 20. 9-Chloro-7- (2fluorophenyl) -5H-pyrimido 5,4-c1 2 benzazepin-2-amine-6-oxyl and 9-chloro-7 (2-fluorophenyl) -N, N-dimethyl. -5 AND-pyrimido C554-d3 2 -benzazepin-2-amine 6-oxide. A solution containing 0.5 g (1.39 mmol) of 8-chloro-1 (2-fluorophenyl) 4- (dimethylamino) methylene-3,4 dihydro-5H-2-benzazepin-5-one-2 oxtand and 0.5 g ( 11.9 mmol) of cyanamide in 6 ml N, K-dimethylformamidle, is heated for 4 hours at 85 ° C. After cooling, the mixture is divided into 75 ml of dichloromethane and 50 ml of hearth. The organic layer is dried and concentrated. The residue is purified by thick-layer chromatography on silica gel using ethyl acetate / methanol (20.ri) as eluent. The strips having Kg 0.5 and 0.7 are removed and recrystallized separately from dichloromethane / methanol to obtain 9-porous 7- (2-fluorophenyl) -5H-pyrimido 5,4-dj 2} benzazepin-2- amine-6-oxide and 9 chloro-7- (2-fluorophenyl) -N, M-dimethyl-5H-pyrimido 5, 4-dJ 2 -benzazope | 2-amine-6-oxide corresponding to iron. 9-Chloro-7- (2-fluorophenyl) -5H-pyrimils) 5,4-dJ 2 -benzazepin-2-amine-6oxide is obtained in the form of Poscept prisms with so pl. 310-350 ° and 9-chloro-7 (2-fluoro-phenyl) -M, M-dimstil-5H-pyr-11, 5, 4-d 2 -bem1zazepin-2-lmi, 16-oxide is obtained in the form of yellow bars with m. square 212-218 (1. Pyrimido-2-benzazepines of the general formula 1 and their pharmacologically compatible acid addition salts are useful pharmaceutical products and are distinguished by pest and anxiety and restlessness. These compounds can be used in The form of the usual pharmaceutical preparations. Table 1 shows the compounds studied, Table 2 shows the results obtained after the tests carried out on the indicated compounds, i experience with a tilt screen, current on the paw, experience on an anesthetized brush and anti-pentametry The tether is a tether test (metrazol) and also indicates appropriate toxicity. Table Substance Compound A 9-Chloro-7- (2-chlorophenyl) -2-methyl-5H-pyrimido 5, 4r-d J 2 Zbenzazepin B 9-Chloro -7- (2-chlorophenyl) -5H, pyrimido 5,4-a 23-benzasej Table 2 14 Continuation of table 1 Substance 9-Chloro-7- (2-fluoro-phenyl) -5N pyrimkdo 5, j-benzazepin-2-amine 9-Chloro-7- (2-fluorophenp) -5-pyrimido 5, 4-a3 2 -bease 9-Chloro-7- (2-fluorofensh1) -N, Ndimethyl-5H-pyrimido 5,4-dj -be zazepin-2 -amine 9-Chloro-7- (2-chlorophenyl) -5HnHpmawoC5, 4-dJC2 3-benzazePIN-6-OXID 8-Chloro-6-phenyl-1,4-dihydro-nHpa3 (wio-f4,3-d3 2 -6eH3a3e8 -Chloro-6- (2-fluorophenyl) -1.4 dihydro 1-methylpyrazolo 4, 3d C2 J-benzazepine 8-Chloro-2-methyl-6-fensh1-2H, 4H-pyrazol-4,3-d) Qz-benzazepine hydrochloride
    orally.
    Thus, the toxicities of all compounds are in the region of the same order of magnitude, with compounds D and, in particular, Z being more toxic than the others. In the experiment with the inclined plane, with the exception of the connection F, no superiority is observed. In the experiment on an unanesthetized cat, the proposed compounds obtained are with the exception of two, and their compounds B and E are more effective than the known substances. In the experience with paw shock and in the metrazole experiment, all the proposed substances are superior in efficiency to the known substances, and the superiority in the metrazole experience is expressed especially well.
    Thus, the proposed compounds not only surpass the known substances in total quantitatively, but also possess a different picture of action, in particular, particularly pronounced efficacy in the metrazol experiment.
    权利要求:
    Claims (2)
    [1]
    1. A method for producing pyrimido 2-benzazepines of the general formula £ or their pharmacologically compatible acid addition salts, characterized in that the compound of the general formula II wherein X and Y have the indicated meanings, P = 0 or 1;
    The R ^ ~ lowering-alkylamino group is reacted with cyanamide in a C ^ -C ^ -alcohol or dimethylformamide medium at 65-120 * С with-> subsequent isolation of the target product in free form or in the form of a salt.
    [2]
    2. The method of obtaining pyrimido-2benzazepines of the general formula £ "SU <", 1181547 where A is one of the groups
    Al is an amino or lower aminoalkyl group;
    X is hydrogen or halogen;
    Y is hydrogen or halogen
    - hydrogen, lower alkyl, amino- or lowering alkylamino group or mercapto group *; ·
    X is hydrogen or halogen; '
    Y is hydrogen or halogen, their pharmacologically compatible acid-addition salts, of which they are different, and that they can be combined with that of the general formula II
    Oh CH-r’i (0) p where X and
    R. = have the indicated meanings; or 1, a lowering alkylamino group is reacted with a compound of the general formula III where R is a mercapto group, or with its acid addition salt, if R '(is hydrogen, lower alkyl, amino or lowering alkylamino group in a C ^ -C ^ -alcohol a solution of Cs-Ccl-alkoxide of an alkali metal, if necessary in the presence of methylene chloride or in formamide at a temperature from room temperature to 100 ° C, followed by isolation of the target product in free form or in the form of a salt.
    Priority featured:
    02/07/79 - the interaction of compound Y, where P = 1 and R ’. - dimethylamino group;
    X and Y are hydrogen or a halogen with an atomic number of maximum 35, with the compound ffl, where R is the amino group ^ 1
    03/01/79 - the interaction of the amino compound, nt or where R (
    C. where R k, where P = 0 and R 'is dimethyl cyanamide or with a compound, where R is a mercapto group, the reaction of the compound If, is dimethylamino, with the compound, R ”is hydrogen, lower alkyl, amino or dimethylamino, moreover. P = 0, if R * is amino, and X and Y are hydrogen or a halogen with atomic number, maximum 35.
    01/22/80 is the interaction of the compound and, where P = 1, is a dimethylamino group, with cyanamide or with compound III, where R is a mercapto group.
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    同族专利:
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    EP0014470B1|1985-07-10|
    DE3070847D1|1985-08-14|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US1011879A| true| 1979-02-07|1979-02-07|
    US1670979A| true| 1979-03-01|1979-03-01|
    CH51080|1980-01-22|
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